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As benzodiazepine exposure increases, mortality risk increases in schizophrenia

Among individuals with schizophrenia, exposure to benzodiazepines was associated with higher mortality, while exposure to antidepressants and antipsychotics was associated with lower mortality.

“The relationship between cumulative antipsychotic exposure and mortality among patients with schizophrenia has been hotly debated during the past decade. Especially in Europe, public media have widely claimed that the shorter life expectancy of patients is attributable to long-term exposure to antipsychotics and that the use of such medications should be avoided whenever possible,” Jari Tiihonen, MD, PhD, of Karolinska Institutet, Stockholm, and colleagues wrote. “Thus far, only two published studies have described the relationship between risk of death and cumulative antipsychotic dose in representative patient populations, but those studies did not control for the effect of concomitant psychotropic medications.”

To investigate the relationship between mortality risk and cumulative antipsychotic, antidepressant and benzodiazepine load, researchers evaluated 21,492 Swedish individuals aged 16 to 65 years diagnosed with schizophrenia. Data from 2006 through 2010 were used to determine all-cause and cause-specific mortality rates.

Moderate antipsychotic exposure (adjusted HR = 0.59; 95% CI, 0.49-0.7), defined as 0.5 mg to 1.5 mg defined daily dose, and high exposure (aHR = 0.75; 95% CI, 0.63-0.89), defined as more than 1.5 mg defined daily dose, were associated with significantly lower overall mortality.

Moderate antidepressant exposure was associated with lower mortality (aHR = 0.85; 95% CI, 0.73-0.98). High antidepressant exposure was associated with even lower mortality (aHR = 0.71; 95% CI, 0.59-0.86).

Benzodiazepine exposure had a dose-response relationship with mortality, with hazard ratios as high as 1.74 (95% CI, 1.5-2.03), according to researchers.

“Our results show that cumulative exposure to benzodiazepines is associated with a substantially higher mortality, and exposure to antipsychotics and antidepressants with moderately lower mortality compared with no use,” Tiihonen and colleagues wrote. “Since it was not possible to fully adjust for severity of illness and lifestyle characteristics, such as smoking and diet, the findings on benzodiazepines may be at least partly attributable to residual confounding… Physicians treating patients with schizophrenia should acknowledge the high mortality associated with chronic high-dose benzodiazepine use.” – by Amanda Oldt

Disclosure: Tiihonen reports serving as a consultant, adviser, or speaker for Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Hoffman-LaRoche, Janssen-Cilag, Lundbeck, Novartis, Organon, Otsuka, and Pfizer, and receiving a grant from the Stanley Foundation. Please see the full study for a list of all authors’ relevant financial disclosures.